Erythropoietin Disequilibrium in Hypertensive Disorders of Pregnancy: Molecular Crosstalk, Placental Hypoxia and Perinatal Consequences

ABSTRACT

Hypertensive disorders of pregnancy (HDP), encompassing gestational hypertension, preeclampsia, and eclampsia, are leading causes of maternal and perinatal morbidity and mortality worldwide. These conditions are characterized by abnormal placentation, impaired uteroplacental perfusion, endothelial dysfunction, and chronic hypoxic stress. Erythropoietin (EPO), a key regulator of erythropoiesis, also exerts cytoprotective, angiogenic, and anti‐inflammatory effects that are essential for normal placental and fetal development. In normal pregnancy, EPO production increases in response to physiological hemodilution and heightened oxygen demand. However, in hypertensive disorders of pregnancy, erythropoietin regulation is frequently disrupted. Evidence indicates that circulating and placental EPO levels may be elevated as a compensatory response to placental hypoxia and maternal anemia, particularly in severe and early‐onset preeclampsia. Conversely, renal impairment and systemic inflammation may blunt erythropoietin synthesis or reduce erythropoietic responsiveness, resulting in functional anemia despite hypoxic stimuli. Altered placental expression of erythropoietin and its receptors further suggests dysregulated signaling pathways that may contribute to impaired angiogenesis and adverse pregnancy outcomes. This narrative review synthesizes current knowledge on erythropoietin physiology in pregnancy and critically examines the mechanisms, clinical significance, and potential biomarker role of altered erythropoietin production in hypertensive disorders of pregnancy. A clearer understanding of these alterations may enhance risk stratification and inform future research aimed at improving maternal and fetal outcomes.